Increased ICAM-1 Expression in the Early Stages of Murine Chronic Graft-versus-Host Disease

Abstract Chronic graft-versus-host disease (cGVHD) is considered to be a model for scleroderma, and vascular changes are considered to be important in that disease. We have examined the expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function associated antigen-1 (LFA-1) using monoclonal antibodies and immunohistochemistry in very early murine cGVHD. ICAM-1 is found on a number of cell types including endothelial cells. It is the natural ligand for LFA-1 found on leukocytes. Adherence of leukocytes to ICAM-1 positive cells is mediated by LFA-1 and this binding is thought to play an important role in a number of cell adhesion events in immune reactions. Experimental cGVHD across minor histocompatibility barriers is established by the iv inoculum of B10.D2 spleen cells into a a sublethally irradiated BALB/c host. Ear and skin biopsies were taken at Days 0-5 and from Days 14 to 120 postinoculum. In comparison to the control group (BALB/c spleen cells given to a sublethally irradiated BALB/c host), the cGVHD mice show increased ICAM-1 expression by Day 3 on endothelial cells and mononuclear cells (MNC) and on fibroblast-like cells by Day 4. By Day 14, there are increasing numbers of ICAM-1-expressing cells and increased epidermal reactivity for ICAM-1; and finally, an increased number of LFA-1 positive infiltrating MNC. These changes wane by Day 28 and are gone by Day 120. These results support the concept that ICAM-1/LFA-1 interactions play a role in the immune regulation of cGVHD. The very early upregulation of ICAM-1 on the endothelium indicates that this cell type may be playing a primary role in cGVHD, and this model should provide a simple system in which to test regulation of endothelial activation in vivo .